The proposed research will define the mechanisms by which leukocytes such as granulocytes, macrophages and small lymphocytes accumulate at sites of immunologically-mediated inflammatory reactions. These studies will be performed in the following manner, using experimental animal model systems in vivo or modifications of the method of Boyden to quantify leukocyte chemotaxis in vitro: 1. Humoral effectors such as the complement, clotting and kinin systems will be studied to determine their role in mediating the accumulation of leukocytes in conditions such as acute inflammation and wound healing. 2. Products derived from cellular immune reactions will be studied as sources of chemotactic factors for macrophages and lymphocytes. The biochemical nature of the factors responsible for the accumulation of inflammatory cells in cellular immune reactions in vivo will be determined. 3. The chemotactic ability of leukocytes from patients with increased susceptibility to infectious, neoplasms and with inflammatory diseases such as rheumatoid arthritis, lupus erythematosus and periodontal diseases will be evaluated. Attempts will be made to correlate defects in leukocyte chemotactic ability with disease expression. 4. The effects of viruses such as Herpes Simplex or Influenza on cellular immune effector function will be studied in vitro. In addition, leukocytes from patients with recurrent Herpes Simplex virus infections or influenza infections will be studied to determine if these viruses alter monocyte or lymphocyte function in man. 5. Factors in serum which modulate monocyte chemotactic responsiveness will be isolated, characterized and studied in patients with inflammatory diseases.